8Q6N

Xanthin riboswitch in complex with oxypurinol

8Q6N の概要

• エントリーDOI: 10.2210/pdb8q6n/pdb
• 関連するPDBエントリー: 7elr
• 分子名称: Xanthin riboswitch NMT-46 (46-MER), Oxypurinol (3 entities in total)
• 機能のキーワード: rna riboswitch xanthin ligand, rna
• 由来する生物種: Ideonella sp. B508-1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15056.07

構造登録者

Nar, H. (登録日: 2023-08-14, 公開日: 2024-08-28, 最終更新日: 2026-03-04)

主引用文献

Hedwig, V.,Sporing, M.,Ottlinger, J.,Kose, S.,Nar, H.,Schnapp, G.,Gottschling, D.,Klein, H.,Aspnes, G.,Klugmann, M.,Hartig, J.S.
Engineering oxypurinol-responsive riboswitches based on bacterial xanthine aptamers for gene expression control in mammalian cell culture.
Nucleic Acids Res., 53:-, 2025

PubMed Abstract: Riboswitch-mediated control of gene expression without the interference of potentially immunogenic proteins is a promising approach for the development of tailor-made tools for biological research and the advancement of gene therapies. However, the current selection of applicable ligands for synthetic riboswitches is limited and strategies have mostly relied on de novo selection of aptamers. Here, we show that the bacterial xanthine I riboswitch aptamer recognizes oxypurinol, the active metabolite of the widely prescribed anti-gout drug allopurinol (Zyloprim®). We have characterized the aptamer/oxypurinol interaction and present a crystal structure of the oxypurinol-bound aptamer, revealing a binding mode similar to that of the cognate ligand xanthine. We then constructed artificial oxypurinol-responsive riboswitches that showed functionality in human cells. By optimizing splicing-based oxypurinol riboswitches using three different strategies, transgene expression could be induced by >100-fold. In summary, we have developed recombinant RNA switches enabling on-demand regulation of gene expression in response to an established and safe drug.

PubMed: 40087885
DOI: 10.1093/nar/gkae1189

実験手法

X-RAY DIFFRACTION (2.63 Å)